反应详情

{7-[(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-benzylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 10 (0.435 g, 0.676 mmol) in tetrahydrofuran (20 mL) is hydrogenated at room temperature and atmospheric pressure over 20% palladium hydroxide on carbon (0.114 g) for 27 hours. The mixture is filtered through Celite, the solid is washed with chloroform, and the combined filtrates concentrated under vacuum. Purification by column chromatography (2:3 ethyl acetate/hexanes) gives {5-amino-7-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}-carbamic acid tert-butyl ester as a solid (0.284 g). 1H NMR (CDCl3): δ 6.61 (bs, 1H), 5.94 (bs, 2H), 4.82–4.69 (bd, 1H), 4.40–4.21 (m, 1H), 4.00–3.59 (m, 3H), 3.55–3.41 (m, 1H), 3.35–3.21 (m, 1H), 2.32–2.08 (m, 1H), 2.01–1.80 (m, 1H), 1.50 (s, 9H), 1.46 (s, 9H), 1.17–1.01 (m, 2H), 0.77–0.63 (m, 2H).

1. customis hydrogenated at room temperature
2. filtrationThe mixture is filtered through Celite
3. washthe solid is washed with chloroform
4. concentrationthe combined filtrates concentrated under vacuum
5. customPurification by column chromatography (2:3 ethyl acetate/hexanes)